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Biomedical subjects

H Niedermüller

Publications and source records attributed to H Niedermüller.

At least 19 recordsLinked to original sources

[Results of experimental gerontology with respect to biological age].

Biological age may be defined as the state of the organism as a whole which is characteristic of the respective chronological age. Objective estimates of biological age are usually obtained by multiple regression analysis of a greater number of age parameters. However, this procedure should be based on a firm knowledge of the regularities of multicellular ageing. By means of a long-term study in male rats regularities of biological ageing have been demonstrated using multiple regression analysis, factor analysis and discriminant analysis. The multiple regression model pointed to an exponential relation between chronological and biological age. By factor analysis it has been shown that the change of the parameters represents to various extents primary ageing and system-specific secondary ageing. The results of discriminant analysis reveal a change in the ageing pattern during senescence. Consequently, test batteries for the objectivation of influences on the rate of ageing should be adapted to the respective phase of ageing in order to obtain maximum sensitivity.

Aging

Effects of aging on the recycling via the pentose cycle and on the kinetics of glycogen and protein metabolism in various organs of the rat.

The rate of metabolic kinetics and the frequency of biological cycles may be correlated with the rate of aging and the maximum life-span potential. Therefore, investigations either into changes with age of such parameters within one species or into differences between species may give some information about the genetic programming of the aging process. Male Sprague-Dawley rats aged 3.5, 7, 12, 17, 23 and 33 months (m) were used to determine the changes with age of those metabolic pathways mentioned in the title, using the liver, kidney, brain, heart and the skeletal muscle. The maximum percentage of glucose utilization via the pentose pathway, compared to the total glucose utilization, was calculated after intravenous administration of D-[1-14C]- and D-[6-14C]glucose by the determination of the trioses (as lipids) 3 hours after the application. Glycogen kinetics was determined analogously. Total protein metabolism was observed using the essential amino acid L-[2,5-3H]histidine. The results indicate a decrease in the glucose utilization via the pentose pathway in the course of aging in liver, kidney, heart and skeletal muscle and a decrease from 3.5 months on in brain, a small but not significant change of the kinetics of glycogen metabolism (a lower turnover), and a reduced rate of protein synthesis in liver, kidney, heart and brain through an age of 23 months, followed by an elevated rate. Brain did not show any changes. The reduction of the pentose pathway may possibly be the cause of higher lipofuscin accumulation in the cells of some organs, lacking sufficient reduction equivalents for lipid metabolism. Furthermore, there could exist a connection with the reduced protein turnover, because less riboses are provided for the synthesis of nucleic acids.

Age Factors

Changes of DNA repair mechanisms during the aging of the rat.

Recent studies have shown a significant reduction in DNA repair capacity in aging rats. Therefore we were interested in investigating which repair mechanism is concerned in this reduction. We investigated: excision repair (ER); single-strand break repair (SSBR); double-strand break repair (DSBR); and gamma-endonuclease susceptibility (ES) by means of the following methods: [3H]thymidine ([3H]dThd) incorporation into DNA after damage by N-methyl-N-nitrosourea (MNU); nucleoid sedimentation after damage by methyl methanesulfonate (MMS); neutral elution techniques after damage by 4-nitroquinoline-1-oxide (NQO); and determination of ES sites by velocity sedimentation in an alkaline sucrose gradient after damage by gamma-irradiation. Studies were done with male Sprague-Dawley rats aged 9, 18 and 28 months using nine different organs. We were able to determine a distinct age dependency of excision repair, a slight reduction of single-strand break repair, an elevation of gamma-endonuclease susceptible sites and no significant change in double-strand break repair in the course of aging. Therefore we see a shift in the pattern of DNA repair: in old age strand break repair mechanisms become more important, while repair replication is reduced. From this we can conclude that genetic expression is altered during the aging process, with all the consequences for the disposition toward certain diseases.

4-Nitroquinoline-1-oxide

[The influence of persistent crowding on the spontaneous motor activity of the aging rat (author's transl)].

In the course of a long-term cohort study of stress and aging, the spontaneous activity of 169 male Sprague-Dawley rats was measured at various ages from 9 to 30 months. 84 animals were submitted to crowding from the age of 5 months onwards by housing them in groups of 12 per Makrolon-IV cage. 85 rats, kept as usual in groups of 6 per makrolon-IV cage, served as a control. Spontaneous activity was assessed by an electronic instrument (Animex Activity Meter), which also enabled us to distinguish between total and large movements. During senescence, the spontaneous activity of the control animals decreased slightly by approximately 20% after the age of 18 months. In addition to the quantitative change, a progressive flattening of the activity rhythm was observed. The animals kept under crowded conditions did not reveal any age-related decrease in spontaneous activity. At an advanced age, this resulted in significantly higher activity values in the crowded group as compared with the controls. The differences appeared even earlier and seemed to be more pronounced in the number of large movements. However, the progressive disappearance of the endogenous rhythm was apparent in both the crowded and the control group. It can be concluded that at least two types of change in the central nervous system may be responsible for the aging-changes in spontaneous activity: one which disintegrates the "time structure" of the organism, and a second one which affects motivational centers. Crowded conditions seem to improve the latter, whereas they have no effect on the aging of the "biological clock".

Age Factors

[The model in experimental gerontology (author's transl)].

In experimental gerontology as a biomedical science, the knowledge and understanding of aging is expressed in hypotheses, theories and models. In this context, the model turns out to be a specific criterion of a definite level of abstraction. The general concept of models comprehends three characteristics: illustration, reduction and pragmatism. Every model is an approximating attempt to comprehend reality. In experimental gerontology various kinds of models can be used. This variety is necessary result of the variety of methods used in this field of science. Any reductionism would imply a restriction, limitation and rigidity. The final aim of experimental gerontology should be the evaluation of a universal dynamic model of aging which is valid for any aging process in biological systems.

Aged

[Aspects of stress and aging in the rat (author's transl)].

Sprague-Dawley rats aged 6 to 22 months were stressed for 2, 16 and 9m resp. by the influence of noise (106 dB, 2h/d) and overcrowding (12 rats/Makrolon-IV-cage). Parameters of the plasma, brain, testicles and the liver (enzymes, metabolites and hormones) and well-known age parameters were evaluated to obtain objective criteria for stress influences. The weights of the whole body and some organs were also measured. The most distinct changes were seen in the plasma enzyme activities CPK, ALD, CHE and AP, in the concentrations of CHO and TRG and in the levels of testosterone, corticosterone and aldosterone. The contraction-relaxation of the tail tendon and the soluble collagen of the corium changed in the direction of higher age, just as lipofuscine content in the brain, cerebellum and the adrenals did. Some activities of enzymes and concentrations of metabolites changed in the brain, liver the testicles. Adrenal weights rose sharply in both stress groups; the body weight was lower. There were some differences in the effects of the two stress factors. These investigations gave some information about the relation between stress and aging and provide a simple means of determining the influence of stress.

Aging

[Gerontological pilot study on learning ability and memory in the stressed rat (author's transl)].

The influence of noise and overcrowding on the learning ability and memory was investigated during a long term cohort study in 120 male Sprague Dawley rats covering an age range from 8 to 14 months. The investigations were performed by means of a semi-automatical multiple-T-maze with 7 choice points. The results showed that noise and overcrowding enhanced the learning ability and memory in rats up to an age of 10 to 12 months. However, the learning ability and memory were declining faster with age in the stressed animals than in the unstressed ones. The stressor "overcrowding" proved to be more effective than the stressor "noise" applied by the authors.

Aging

[Discriminant analysis of age parameters of the rat (author's transl)].

The capacity of age parameters to discriminate between groups or individuals of different biological age was investigated in the course of a long-term cohort study. 23 age parameters measured in 71 male Sprague-Dawley rats at the ages of 10, 17, 25 and 30 months, were submitted to a stepwise discriminant analysis. An optimal simultaneous discrimination between the four age groups was obtained by 3 discriminant functions with scores of 89.8%, 6.2% and 4%, with a correct classification of 98,6% of all individuals. Three analyses of successive age groups (10--17, 17--25, 25--30 months) resulted in a 100% correct classification by one function each. However, it turned out that in different phases of senescence an optimal discrimination between individuals or groups of different biological age is obtained by distinct combinations and weights of the parameters.

Aging

[Problems of the assessment of biological age (author's transl)].

Biological age may be defined at the state of the organism as a whole which is characteristic of the respective chronological age. Usually, it is estimated by multivariate analysis of a battery of age parameters. However, this procedure requires the knowledge of the regularities of multicellular ageing since interferences about the behaviour of the total system from its subsystems may only drawn when the regularities of the total system are understood. By means of the ageing of the rat, the possibility is demonstrated to study these regularities by factor analysis. As a result, primary and system-specific secondary aging processes are postulated which are expressed to various extents in the individual age parameters.

Aging

[A mathematical model of the kinetics of collagen metabolism in the tendons and skin of young and old rats].

Two groups of 60 male Sprague-Dawley rats aged 3 and 20-24 months respectively were used to establish a 3-compartmentmodel of the kinetics of the collagen metabolism in the tail tendon and skin by means of tritium labelled L-prolin. The 3 compartments were divided into pro- and tropocollagen, labile polymer collagen and stabile polymer collagen respectively. The results suggest the following conclusions concerning the metabolism and ageing of the collagens investigated: 1. Collagen of the tendon and collagen of the skin reveal different dynamics of metabolism. 2. Stabile and labile polymeric collagen originate from different tropocollagens. 3. Both intracellular and extracellular processes are responsible for the age-changes of tendon- and skin-collagen.

Aging

[Gerontological investigations of the nucleic acid metabolism in the rat. II. DNA repair capacity in different ages (authors transl)].

We tried to develop a model of in-vivo investigations into the DNA repair capacity of rats and, by means of this model, to determine the effect of age. To this end the DNA repair capacity was determined after gamma-irradiation with 3 groups of male white Sprague-Dawley rats aged 6, 18-20 and 32-34 months. The organs liver, kidney, heart and spleen were used for this investigation. The relative repair (RR) showed a discontinuous course both in the 4 organs, and in the 3 different age groups. We define "relative repair" as the relationship between the specific activity of DNA decomposition products and the specific activity of DNA in an irradiated test group, as compared with an unirradiated control group. In all age groups the course was similar in the liver and the spleen, especially in the young rats, as well as in the heart and the kidney. Age differences were seen to be significant in all 4 organs at particular intervals after the irradiation, which means that the maximum relative repair occurs at different times. The integration over the whole course of the investigation shows a distinct reduction in the relative repair with increasing age in all the investigated organs except the spleen, where we could not see a difference between the 2 older groups.

Age Factors

[Tensibility measurements on the rat's aorta III. Analysis of longitudinal and transversal extension as related to age (authors transl)].

Stress-strain diagrams of standardizised longitudinal and transversal stripes of the thoracic aorta of 125 male Sprague-Dawley rats aged 9, 15, 24 and 30 months were recorded by an electromechanical instrument. The stripes were subjected to three successive extension-relaxation cycles. The relaxation curves of the third cycle were approximated to the functions y = a + bx and y = cxd (longitudinal stripes) and y = mxf and y = gxh (transversal stripes) respectively. The parameters could be interpreted as measures for structural and functional properties of elastic and collagenous fibers. The age changes of the curve parameters led to the following conclusions concerning age-dependent functional alterations of the aorta: The emphasis can be placed upon the increasing resistance counteracting the extension occuring with great stroke volumes. This may lead to the reduction of the capacity of the air chamber with great stroke volumes. These phenomena seem to be mainly caused by an increase of the pitch of the spiral of the collagenic fiber and the increase of the amount and/or the stability of the collagen. Age-related alterations of the elastin and of the net structure formed by the fibers influence also the distensibility at smaller extensions but seem to be less important. Therefore, the structural alterations of the aorta with age will affect the function in the first place at large stroke volumes and not be very obvious at a basic heart performance.

Age Factors

[The motor activity as an age parameter of the rat (authors transl)].

The motor activity as an behavioural parameter provides information about the functional state of the organism as a whole. Therefore it is an important age parameter. The results of activity measurements, however, depend strongly on the method of registration. Using 3 groups of male Sprague-Dawley rats aged 9, 15 and 29 months two methods have been tested: 1) An electronic recording: the rats were registrated in their normal cages on the Animex-Activity-Meter during the dark-phase in complete darkness. The activity measured by this method has been regarded as spontaneous activity. 2) A kinematographic method: the rats were registrated in a changed environment at constant light during the dark-phase. The activity assessed by this method has been regarded as reactive activity. Spontaneous and reactive activity show a different age dependence. For the use of the motor activity as an age parameter, both, spontaneous and reactive activity, should be assessed to get a better information about the ageing of the different functional levels of the systems governing the animal's behaviour.

Aging